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LETTERER-SIWE'S SYNDROME: REPORT OF A CASE
WITH UNUSUAL PERIPHERAL BLOOD CHANGES
BY
N. P. ORCHARD, M.B., B.S.
From St. James Hospital, Balham, London
(RECEIVED FOR PUBLICATION, DECEMBER 20, 1949)
In 1933 Siwe laid down the criteria of the
syndrome now called Letterer-Siwe disease, and in
the literature before and after that date the different
features are discussed and related to the reported
cases. The following case illustrates in particular
the peripheral blood changes which may occur in
this condition, and a table is appended summarizing
the clinical and pathological features of 18 cases
beginning with Letterer's (1924) case and bringing
the series up to date (1950) with the present case.
Case Report
A boy aged 3j years was admitted on March 11, 1948,
with a history of soreness of the right ankle, anorexia,
insomnia, and screaming in the night. The temperature
was normal. The child was very pale and had puffy eyes.
Firm and discrete nodes approximately 0 75 cm. in
diameter were palpable in the neck, especially in the
posterior triangle, the axillae, and the groins. The tip
of the spleen was easily palpable but there was some
doubt about the liver being palpable. The right ankle
was swollen but there was no tenderness and the movements were neither limited nor painful.
A radiograph of the chest showed a doubtful hilar
shadow; the skull, humeri, pelvis, femora, tibiae and
fibulae were normal.
Blood Count:
Haemoglobin, 44% (Haldane).
R.B.C., 2,300,000 per c.mm. W.B.C., 7,000 per
c.mm.
Differential white count: neutrophil polymorphs,
4% (280 per c.mm.), lymphocytes, 95% (6,650 per
c.mm.), haemohistiocytes, 1% (70 per c.mm.).
A tentative diagnosis of aleukaemic lymphatic
leukaemia was made. During the next fortnight the
temperature ranged from 90°-100° F. and a mass became
palpable in the left iliac fossa.
28.3.48. Sternal puncture was performed. In the
marrow films haemohistiocytes dominated the picture.
Very few mature lymphocytes, granulocytes, and normoblasts were to be seen.
29.3.48. Intramuscular penicillin (20,000 units fourhourly) was started.
Wassermann reaction + +; Kahn reaction, strong
positive.
Volmer patch test negative after 48 hours.
Total serum protein 5 55 g. %.
3 83 g. %.
Albumin
Globulin
1-72 g. %.
Albumin/globulin ratio 2^ 2: 1.
The father's and mother's Wassermann and Kahn
reactions were negative.
Transfusion of 1 pint of packed cells.
6.4.48. Wassermann + +; Kahn, strong positive.
7.4.48. Penicillin dosage increased to 50,000 units
four-hourly.
11.4.48. Wassermann and Kahn tests negative.
Paul Bunnell test negative.
22.4.48. Penicillin discontinued.
20.5.48. X-ray examination of the humeri, pelvis,
femora, tibiae, and fibulae showed no abnormality.
26.5.48. Transfusion of 1 pint of blood. The spleen
was easily palpable but not the liver, owing to guarding
in the right hypochondrium. By percussion the liver was
found to be enlarged two fingerbreadths below the costal
margin.
17.6.48. Biopsy of a lymph node from the posterior
triangle.
18.6.48. Liver palpable now.
19.6.48. Child vomited a few ounces of bright blood.
20.6.48. Occult blood in the stools. Transfusion of
1 pint of packed cells. Patient now running a hectic
temperature.
24.6.48. Report on section of the lymph gland
diagnosed reticulum cell medullary reticulosis.
30.6.48. Haemoglobin level falling rapidly.
4.7.48. Pallor now very marked, and ulcerative angina
well established. The spleen and liver were larger than
before.
9.7.48. Haemorrhagic gingivitis.
11.7.48. Patient died.
The clinical features of this and other reported cases
are summarized in Table 1.
151
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152
ARCHIVES OF DISEASE IN CHILDHOOD
9.
.6
4
x
FIG. 4.-Smear of a lymph node showing large numbers
of reticulum cells which are identical with the
haemohistiocytes seen in Fig. 2. Leishman. x 675.
675.
RR
-lw
-Mft.
Anr..
4w.
FIG. 2.-Peripheral blood smear showing binucleate
form of haemohistiocyte which was present in
appreciable numbers. Leishman. x 1200.
FIG. 5.-Lung showing alveolar septa
thickened and infiltrated by reticulum cells.
toxylin and eosin. x 100.
markedly
Haema-
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153
LETJlERER-SI WE'S SYNDROME
TABLE 1
SUMMARY OF BLOOD FINDINGS IN PRESENT CASE
Differential White Count
o
Date
Hb. |W.B.C. i
R.B.C.
(millions (Haldane) (millions
()
per c.mm.)
per c.mm.)
7,000
o
I-
280
14,,,
16
40
21, ,,
29, ,,
1i 6
38
1, ,,
3-5
68
4,000
360
,,11, ,,
3 5
68
5,400
864
18, ,,
2*5
48
5,800
116
28, ,,
3 0
64
4,200
84
May
16, ,,
2-3
50
6,500
130
,,
21, ,,
2-2
50
5,200
104
,,
April
I
3,900
1 °AB
0
CZ
-
70
+.
Z
44
3,500
C.)
0
2-3
March 11, 1948
0
0
-
6,650
3,080
3,042
70
35
-
195
-
-
315
-
663
Transfusion of one pint of packed cells
26, ,,
40
3,520
80
Transfusion of one pint of blood
June
9, ,,
3 2
62
6,300
252
-
4,158
-
1,890
,
18, ,,
20, ,,
2-4
46
3,100
124
-
2,325
-
651
25, ,,
3-2
2,720
-
578
,
Transfusion of one pint of packed cells
62
3,400
1102
-
-
* The primitive cells in the peripheral blood were classed as haemohistiocytes. They were 15-25,u in diameter, having a large
round reticular nucleus, a number containing nucleoli. The cytoplasm was abundant and of a pale dirty blue colour (Leishman stain).
Some cells had cytoplasmic vacuoles and others fixed pseudopodia.
Post-mortem Report
External Appearance. A very pale and emaciated
male child. The oral cavity showed ulcerative angina
and gingivitis.
Chest. Oesophagus. Nil.
Thymus. Small and macroscopically normal.
Pleura. Left pleural sac contained one pint of yellow
fluid.
Larynx. Nil.
Lung. Trachea and bronchi normal. Lungs pale:
superficial area of collapse right lower lobe.
Pericardium. Nil.
Heart. Sub-pericardial haemorrhages near the apex
and in the auricles.
Valves. Nil.
Vessels. Nil.
Abdomen. Peritoneum. Nil.
Stomach. Mucosa very pale.
Duodenum. Nil.
Bile ducts. Patent.
Intestines. Peyer's patches not enlarged; solitary
lymph follicles of the colon were prominent.
Lymph Nodes. The cervical, axillary, pancreaticosplenic, external iliac and inguinal glands were red and
varied in size from 0 75-1 cm. in diameter.
Spleen. Weight, 100 g. Cut surface dark red and
firm.
Liver. Weight, 500 g. Dark terracotta colour.
Structure appeared normal.
Pancreas. Nil.
Kidneys. Weight, 20 oz. Capsules stripped easily
leaving a smooth surface. The cut surface was very pale.
Genito-Urinary Tract. Nil.
Brain. Very pale and macroscopically normal.
Spinal Cord. Not examined.
The sternal, vertebral, and femoral marrow was of a
greyish pink colour.
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154
ARCHIVES OF DISEASE IN CHILDHOOD
Discussion
Summary
This is a case of reticulum cell medullary
An unusual case of reticulum cell medullary
teticulosis with peripheral blood changes. The reticulosis displaying the features of the Lettererwhite blood count fluctuated between a low normal Siwe syndrome is described. A tabular review of
and frank leucopenia, with the lymphocyte as the the cases reported in the literature is presented in the
predominant cell; a fair number of haemohistio- Appendix.
cytes were invariably present. The reticulum cells
thanks are due to Dr. B. Barling for permission
showed unmistakable differentiation in two direc- to My
the case, and to Dr. A. H. T. Robb-Smith
tions, namely, haemic and histiocytic. Without a for publish
his helpful criticism and encouragement.
doubt the haemohistiocytes in the peripheral blood
and in the marrow were similar to the proliferating
REFERENCES
reticulum cells in the lymph glands, spleen, liver, Abt, A. F., and Denenholz, E. J. (1936). Amer. J. Dis.
lungs, and kidney. They were medullary reticulum
Child., 51, 499.
cells with a tendency, as far as the nuclear structure Akiba, R. (1926). Virchows Arch., 260, 262.
was concerned, towards haemic differentiation. Creveld, S. van, and Ter Poorten, F. H. (1935). Arch.
Dis. Childh., 10, 125.
Definite evidence of differentiation towards histio- Foot, N.
C., and Olcott, C. T. (1934). Amer. J. Path.,
cytes was to be seen in the liver, spleen, lungs,
10, 81.
kidney, and, to a lesser extent, in the lymph nodes. Gittins, R. (1933). Arch. Dis. Childh., 8, 367.
Apart from a few departures from the accepted Guizetti, H. U. (1931). Virchows Arch., 282, 194.
picture of the Letterer-Siwe syndrome (namely, the
presence of haemohistiocytes in the peripheral
blood, and the absence of purpura and osseous
changes) the case reported satisfies the criteria laid
down by Siwe. The Wassermann and Kahn
reactions were strongly positive on two occasions
but negative on the third. This no doubt was due
to the change in the plasma globulin.
Klostermeyer, W. (1934). Beitr. path. Anat., 93, 1.
Krahn, H. (1926). Dtsch. Arch. klin. Med., 152, 179.
Letterer, E. (1924). Z. Pathol., 30, 377.
Podvinec, E., and Terplan, K. (1931). Arch. Kinderheilk., 93, 40.
Roussy, G.. and Oberling, C. (1934). Wien. med. Wschr.,
84, 407.
Sherman, I. (1929). Arch. Path., 7, 78.
Siwe, S. A. (1933). Z. Kinderheilk., 55, 212.
Uher, V. (1933). Virchows Arch., 289, 504.
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LETJTERER-SI WE'S SYNDROME
155
A'PPENDIX
ANALYSIS OF FEATURES OF REPORTED AND PRESENT CASES
Reticulosis of
Clinical Features
Age
Author
of
Patient
Letterer (1924)
6 mths.
Organs
"1
Pentng
Signs
Purpura
-e&mU)11I wks.
+
-
+
+
+
-
I+4+ +
+
None clinically
to~ O
co
Osseous
Change
++ + + + +
sepsis
Akiba (1926)
10Omths.
Krahn (1926)
Sherman (1929)
5 years
il days
Guizetti (1931)
±
_++
+
,,
,
+
, ++ ,
,,
,
Purpura
sepsiss
Sepsis
6 wks.
+
6 mths.
+
Jaundice
4 days
+
-
+
-
+
S
-
3 mths.
Cough,
fever,
epistaxis
21 days
+
-
+
+
-
?
Podvinec and Terplan
1 year
Fever
14 days
+
+
-
-
+
Uher (1933)
1 years
+
+
+
-
S
+
+
+
Siwe (1933)
16 mths.
Sore throat,* 17 days
fever
Swelling of 4 mths.
the left leg
+
-
S
+
+
+I Cysticchanges in the
+
-
(1931)
CGittins (1933)
(a)
(b)
(C)
(d)
Klostermeyer (1934)
Ths^st anti Okntt
23 mths.
erysipelasI
Anaemia
21lmths. Anaemia
abscesses
Anaemia
1 year
17 wka.
Anaemia
13 mtha.
Swelling of
+
24, mths.
3 wks.
+
-
+
-
:++ ±+ S
+ i++ +
11 days
4 mths.
?
-
-
7 wks.
+
+
the face
95sas
Po.qcWr,,ira,,~
+
+
+
-
,,
9,
left fibula on x-ray
examination
-
+
+
- ++ +
S ++ +
+
+± ++ Slight x-ray changes
-
+
+
A
-
-
++
?
++
+J
++ ++ ++ '
?
+
+ + ++
++ ++ Cysticchanges in the + + ++ ++ +±1 +
right humerus on
x-ray examination
+ + + + None clinically
++ ++ ++ + +
+
11
otiti s m'e`dia
(1934)
±
+
?
None clinically
,
,
_+±+ Nonedcinically
,,
+±+ +
mi
++ + ++ + ++
± + ++ + ±±
++4 +± ±
+
±
+
+
+
+ - ++ +
+ !+ +& +
+ ++
+
?
?
?
+
?
,
revealed ra-re-fa-ction
of the pelvis, upper
end of the right
femur. Osteoporosis,
of the spine at first
suggested Pott's dis-
++++ +
+
±
ease
Roussy and Oberling
(1934)
8 mths.
Purpura
1 mth.
+
-
+
+
S
+
van Creveld and
Ter Poorten (1935)
4 mths.
Otitis media
8 wks.
+
-
-
-
S
+
Abt and Denenholz
2 years
++ +
+
+
None clinically
Cysticchanges in the
skull, head of the
right humerus and
lower end of the right
++ + ++ + + + +
+ ++ +
+ ++
femur
mths.
+
-
Swelling of 4 mths.
right ankde,II
anorexia,
+
+ IS
Tumour of
the skull
4i-
+
±
±
±± ±±+ Pulsatinat tumour of -l-
I
i-1-1
++ A
+
+
+
the skull. On x-ray
examination a cystic
±±
±±++
±±i-4- ±
area wasq annarent
----
INone clinically
+
++~++
insomnia
6..
?=Not mentioned.S=Slight.
?=Not mentioned.
A=agranulocytosis.
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Letterer-Siwe's Syndrome: Report
of a Case with Unusual Peripheral
Blood Changes
N. P. Orchard
Arch Dis Child 1950 25: 151-155
doi: 10.1136/adc.25.122.151
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